Online ISSN: 1945-4589
Learn about our FREE Post-Publication Promotion Services

Aging-US: GPA peptide inhibits NLRP3 inflammasome activation to ameliorate colitis

11-10-2020

Aging-US recently published "GPA peptide inhibits NLRP3 inflammasome activation to ameliorate colitis through AMPK pathway" which reported that pyroptosis and NLRP3 inflammasome are associated with various kinds of inflammatory diseases including colitis.

In vivo, the authors found GPA peptide could exert anti-inflammatory effects on DSS-induced mice colitis, and its anti-inflammatory effects are abolished in NLRP3-/- mice.

In macrophage, GPA suppresses the assembly of NLRP3 inflammasome and GSDMD cleavage.

Furthermore, GPA maintains mitochondrial homeostasis through inhibiting ROS, mtDNA and NLRP3 mitochondrial localization, with other signals related to NLRP3 inflammasome unaffected.

The Aging-US results suggest that GPA inhibits NLRP3 inflammasome activation through increasing AMPK phosphorylation to suppress ROS, and can be applied in the prevention of colitis through targeting NLRP3.

"The Aging-US results suggest that GPA inhibits NLRP3 inflammasome activation through increasing AMPK phosphorylation to suppress ROS, and can be applied in the prevention of colitis through targeting NLRP3"

Dr. Jian Peng from The Department of Animal Nutrition and Feed Science at The College of Animal Science and Technology within Huazhong Agricultural University as well as The Cooperative Innovation Center for Sustainable Pig Production - both in Wuhan, Hubei, China said, "Ulcerative colitis (UC) is a chronic and idiopathic inflammatory disease that affects colon, resulting in weight loss, diarrhea, rectal bleeding, and abdominal pain."

Pyroptosis, an inflammatory cell death, can lead to cell membrane rupture, then ends to the release of cell contents and a large number of inflammatory factors, such as IL-1β and IL-18.

Figure 7. Putative mechanism for the anti-inflammatory effect of GPA in macrophages. GPA increased AMPK phosphorylation to suppress ROS and mtDNA production, resulting in the blocking of NLRP3 mitochondrial translocation, which inhibited NLRP3 inflammasome activation and pyroptosis.

Pyroptosis activation coordinates mucosal immune to defend intestines from infection, resulting in infected epithelial cells extrusion, and the fact that infected epithelial cells or macrophages are swallowed by neutrophils.

Meanwhile, pyroptosis is overactivated in macrophages, it results in the production of a large number of pro-inflammatory cytokines, followed by the activation of immune cells in the lamina propria, and the disruption of the intestinal epithelial structure and intestinal homeostasis.

However, in an intestinal pathological condition, ROS, as signal molecules, activate the inflammatory pathway to amplify inflammatory response and damage the intestinal structure.

Meanwhile, in intestinal macrophages, ROS, as a molecular signal, activates the NLRP3 inflammasome and secrete IL-1β and IL-18, resulting in pyroptosis and amplification of inflammatory response.

The Peng Research Team concluded in their Aging-US Research Paper, "GPA ameliorates DSS-induced colitis in a NLRP3-dependent manner. GPA increases the phosphorylation of AMPK, where it blocks ROS and mtDNA production as well as NLRP3 mitochondrial translocation, leading to suppressing NLRP3 inflammasome activation and pyroptosis in macrophages (Figure 7). Our results suggest that GPA could be potentially used for the prevention of colitis."

Full Text - https://doi.org/10.18632/aging.103825

Correspondence to: Jian Peng email: pengjian@mail.hzau.edu.cn

Keywords: GPA, NLRP3, AMPK, ROS, colitis

About Aging-US:

Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases.

Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

Please visit our website at www.Aging-US.com and connect with us:

For media inquiries, please contact media@impactjournals.com.